Journal ArticleDOI
Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20
Melanie Bahlo,David R. Booth,Simon A. Broadley,Matthew A. Brown,Matthew A. Brown,Simon J. Foote,Lyn R. Griffiths,Trevor J. Kilpatrick,Trevor J. Kilpatrick,Jeanette Lechner-Scott,Pablo Moscato,Victoria M. Perreau,Justin P. Rubio,Rodney J. Scott,Rodney J. Scott,Jim Stankovich,Graeme J. Stewart,Bruce V. Taylor,James S. Wiley,Glynnis Clarke,Mathew B Cox,Peter A. Csurhes,Patrick Danoy,Karen E. Drysdale,Judith Field,Judith M. Greer,Preethi Guru,Johanna Hadler,Brendan J. McMorran,Cathy J Jensen,Laura J. Johnson,Ruth McCallum,Marilyn E. Merriman,Tony R. Merriman,Karen Pryce,Lotfi Tajouri,Ella J Wilkins,Brian L. Browning,Sharon R. Browning,D. I. Perera,Simon Broadley,Helmut Butzkueven,Helmut Butzkueven,William M. Carroll,Caron Chapman,Allan G. Kermode,Mark Marriott,Deborah F. Mason,Robert Heard,Michael P. Pender,Michael P. Pender,Mark Slee,Niall Tubridy,Ernest Willoughby +53 more
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To identify multiple sclerosis (MS) susceptibility loci, a genome-wide association study in 1,618 cases and used shared data for 3,413 controls and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15.Abstract:
To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).read more
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Mechanisms underlying inflammation in neurodegeneration.
TL;DR: There is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators in neurodegenerative diseases.
Journal ArticleDOI
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
Stephen Sawcer,Garrett Hellenthal,Matti Pirinen,Chris C. A. Spencer,Nikolaos A. Patsopoulos,Nikolaos A. Patsopoulos,Nikolaos A. Patsopoulos,Loukas Moutsianas,Alexander T. Dilthey,Zhan Su,Colin Freeman,Sarah E. Hunt,Sarah Edkins,Emma Gray,David R. Booth,Simon C. Potter,An Goris,Gavin Band,Annette Bang Oturai,A. Strange,Janna Saarela,Céline Bellenguez,Bertrand Fontaine,Matthew W. Gillman,Bernhard Hemmer,Rhian Gwilliam,Frauke Zipp,Alagurevathi Jayakumar,Roland Martin,Stephen Leslie,Stanley Hawkins,Eleni Giannoulatou,Sandra D'Alfonso,Hannah Blackburn,Filippo Martinelli Boneschi,Jennifer Liddle,Hanne F. Harbo,Hanne F. Harbo,M. Perez,Anne Spurkland,Matthew Waller,Marcin P. Mycko,Michelle Ricketts,Manuel Comabella,Naomi Hammond,Ingrid Kockum,O. T. McCann,Maria Ban,Pamela Whittaker,Anu Kemppinen,Paul A. Weston,Clive Hawkins,Sara Widaa,John Zajicek,John Zajicek,Serge Dronov,Neil Robertson,Suzannah Bumpstead,Lisa F. Barcellos,Lisa F. Barcellos,Rathi Ravindrarajah,Roby Abraham,Lars Alfredsson,Kristin G. Ardlie,Cristin Aubin,Amie Baker,K Baker,Sergio E. Baranzini,Laura Bergamaschi,Roberto Bergamaschi,Allan L. Bernstein,Achim Berthele,Mike Boggild,Jonathan P. Bradfield,David Brassat,Simon Broadley,Dorothea Buck,Helmut Butzkueven,Ruggero Capra,William M. Carroll,Paola Cavalla,Elisabeth Gulowsen Celius,Sabine Cepok,Rosetta M. Chiavacci,Françoise Clerget-Darpoux,Katleen Clysters,Giancarlo Comi,Mark D. Cossburn,Isabelle Cournu-Rebeix,M. B. Cox,Wendy Cozen,Bruce A.C. Cree,Anne H. Cross,Daniele Cusi,Mark J. Daly,Mark J. Daly,Emma J. Davis,Paul I.W. de Bakker,Paul I.W. de Bakker,Paul I.W. de Bakker,Marc Debouverie,Marie B. D'hooghe,K Dixon,Rita Dobosi,Bénédicte Dubois,David Ellinghaus,Irina Elovaara,Federica Esposito,Claire Fontenille,Simon J. Foote,Andre Franke,Daniela Galimberti,Angelo Ghezzi,Joseph T. Glessner,Refujia Gomez,Olivier Gout,Colin A. Graham,Struan F.A. Grant,Struan F.A. Grant,Franca Rosa Guerini,Hakon Hakonarson,Hakon Hakonarson,Per Hall,Anders Hamsten,Hans-Peter Hartung,Robert Heard,Simon Heath,Jeremy Hobart,Jeremy Hobart,Muna Hoshi,Carmen Infante-Duarte,Gillian Ingram,Wendy Ingram,Wendy Ingram,Talat Islam,Maja Jagodic,Michael Kabesch,Allan G. Kermode,Trevor J. Kilpatrick,Cecilia Kim,Norman Klopp,Keijo Koivisto,Malin Larsson,Mark Lathrop,Jeannette Lechner-Scott,Maurizio Leone,Virpi M. Leppä,Ulrika Liljedahl,Izaura Lima Bomfim,Robin R. Lincoln,Jenny Link,Jianjun Liu,Åslaug R. Lorentzen,Åslaug R. Lorentzen,Sara Lupoli,Fabio Macciardi,Fabio Macciardi,Thomas M. Mack,Mark Marriott,Vittorio Martinelli,Deborah F. Mason,Jacob L. McCauley,Frank D. Mentch,Inger-Lise Mero,Tania Mihalova,Xavier Montalban,John Mottershead,Kjell-Morten Myhr,Paola Naldi,William E R Ollier,Alison Page,Aarno Palotie,Jean Pelletier,Laura Piccio,Trevor Pickersgill,Fredrik Piehl,Susan Pobywajlo,Hong L. Quach,Patricia P. Ramsay,Mauri Reunanen,Richard Reynolds,John D. Rioux,John D. Rioux,Mariaemma Rodegher,Sabine Roesner,Justin P. Rubio,Ina-Maria Rueckert,Marco Salvetti,Erika Salvi,Adam Santaniello,Catherine Schaefer,Stefan Schreiber,Christian Schulze,Rodney J. Scott,Finn Sellebjerg,Krzysztof Selmaj,David Sexton,Ling Shen,Brigid Simms-Acuna,Sheila Skidmore,Patrick M. A. Sleiman,C. Smestad,Per Soelberg Sørensen,Helle Bach Søndergaard,Jim Stankovich,Richard C. Strange,Anna-Maija Sulonen,Emilie Sundqvist,Ann-Christine Syvaenen,Francesca Taddeo,Bruce V. Taylor,Jenefer M. Blackwell,Jenefer M. Blackwell,Jenefer M. Blackwell,Pentti J. Tienari,Elvira Bramon,Ayman Tourbah,Matthew A. Brown,Ewa Tronczynska,Juan P. Casas,Niall Tubridy,Aiden Corvin,Jane Vickery,Jane Vickery,Janusz Jankowski,Pablo Villoslada,Hugh S. Markus,Kai Wang,Christopher G. Mathew,James Wason,Colin N. A. Palmer,H-Erich Wichmann,H-Erich Wichmann,Robert Plomin,Ernest Willoughby,Anna Rautanen,Juliane Winkelmann,Michael Wittig,Richard C. Trembath,J. Yaouanq,Ananth C. Viswanathan,Ananth C. Viswanathan,Haitao Zhang,Nicholas W. Wood,Rebecca L. Zuvich,Panos Deloukas,Cordelia Langford,Audrey Duncanson,Jorge R. Oksenberg,Margaret A. Pericak-Vance,Jonathan L. Haines,Tomas Olsson,Jan Hillert,Adrian J. Ivinson,Philip L. De Jager,Philip L. De Jager,Philip L. De Jager,Leena Peltonen,Graeme J. Stewart,David A. Hafler,David A. Hafler,Stephen L. Hauser,Gil McVean,Peter Donnelly,Peter Donnelly,Alastair Compston +265 more
TL;DR: In this article, a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, they have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci.
Journal ArticleDOI
An Abundance of Rare Functional Variants in 202 Drug Target Genes Sequenced in 14,002 People
Matthew R. Nelson,Daniel Wegmann,Margaret G. Ehm,Darren Kessner,Pamela L. St. Jean,Claudio J. Verzilli,Judong Shen,Zheng-Zheng Tang,Silviu Alin Bacanu,Dana Fraser,Liling Warren,Jennifer L. Aponte,Matthew Zawistowski,Xiao Liu,Hao Zhang,Yong Zhang,Jun Li,Yun Li,Li Li,Peter Woollard,Simon Topp,Matthew D. Hall,Keith Nangle,Jun Wang,Gonçalo R. Abecasis,Lon R. Cardon,Sebastian Zöllner,John C. Whittaker,Stephanie L. Chissoe,John Novembre,Vincent Mooser +30 more
TL;DR: It is concluded that because of rapid population growth and weak purifying selection, human populations harbor an abundance of rare variants, many of which are deleterious and have relevance to understanding disease risk.
Journal ArticleDOI
Vitamin D and Multiple Sclerosis
TL;DR: The results of these studies support a protective effect of vitamin D, but there are uncertainties and many unanswered questions, including how vitamin D exerts a Protective effect, how genetic variations modify the effect, and whether vitamin D can influence the course of MS progression.
Journal ArticleDOI
Gender differences in autoimmune disease.
TL;DR: Gender differences in systemic and organ-specific autoimmune diseases are considered, and human data is summarized that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed.
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